Cryo-EM reveals cholesterol binding in the lysosomal GPCR-like protein LYCHOS.
Zhao, J., Shen, Q., Yong, X., Li, X., Tian, X., Sun, S., Xu, Z., Zhang, X., Zhang, L., Yang, H., Shao, Z., Xu, H., Jiang, Y., Zhang, Y., Yan, W.(2025) Nat Struct Mol Biol 
- PubMed: 39824976 
- DOI: https://doi.org/10.1038/s41594-024-01470-9
- Primary Citation of Related Structures:  
8Y56 - PubMed Abstract: 
Cholesterol plays a pivotal role in modulating the activity of mechanistic target of rapamycin complex 1 (mTOR1), thereby regulating cell growth and metabolic homeostasis. LYCHOS, a lysosome-localized G-protein-coupled receptor-like protein, emerges as a cholesterol sensor and is capable of transducing the cholesterol signal to affect the mTORC1 function. However, the precise mechanism by which LYCHOS recognizes cholesterol remains unknown. Here, using cryo-electron microscopy, we determined the three-dimensional structural architecture of LYCHOS in complex with cholesterol molecules, revealing a unique arrangement of two sequential structural domains. Through a comprehensive analysis of this structure, we elucidated the specific structural features of these two domains and their collaborative role in the process of cholesterol recognition by LYCHOS.
Organizational Affiliation: 
Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.